tbuckley/cabot-search huggingface dataset:
National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH)
Authors: Funda Meric-Bernstam, James M. Ford, Peter J. O'Dwyer, Geoffrey I. Shapiro, Lisa M. McShane, Boris Freidlin, Roisin E. O'Cearbhaill, Suzanne George, Julia Glade-Bender, Gary H. Lyman, James V. Tricoli, David Patton, Stanley R. Hamilton, Robert J. Gray, Douglas S. Hawkins, Bhanumati Ramineni, Keith T. Flaherty, Petros Grivas, Timothy A. Yap, Jordan Berlin, James H. Doroshow, Lyndsay N. Harris, Jeffrey A. Moscow
Journal: Clinical Cancer Research (2023)

Abstract Over the past decade, multiple trials, including the precision medicine trial National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH, EAY131, NCT02465060) have sought to determine if treating cancer based on specific genomic alterations is effective, irrespective of the cancer histology. Although many therapies are now approved for the treatment of cancers harboring specific genomic alterations, most patients do not respond to therapies targeting a single alteration. Further, when antitumor responses do occur, they are often not durable due to the development of drug resistance. Therefore, there is a great need to identify rational combination therapies that may be more effective. To address this need, the NCI and National Clinical Trials Network have developed NCI-ComboMATCH, the successor to NCI-MATCH. Like the original trial, NCI-ComboMATCH is a signal-seeking study. The goal of ComboMATCH is to overcome drug resistance to single-agent therapy and/or utilize novel synergies to increase efficacy by developing genomically-directed combination therapies, supported by strong preclinical in vivo evidence. Although NCI-MATCH was mainly comprised of multiple single-arm studies, NCI-ComboMATCH tests combination therapy, evaluating both combination of targeted agents as well as combinations of targeted therapy with chemotherapy. Although NCI-MATCH was histology agnostic with selected tumor exclusions, ComboMATCH has histology-specific and histology-agnostic arms. Although NCI-MATCH consisted of single-arm studies, ComboMATCH utilizes single-arm as well as randomized designs. NCI-MATCH had a separate, parallel Pediatric MATCH trial, whereas ComboMATCH will include children within the same trial. We present rationale, scientific principles, study design, and logistics supporting the ComboMATCH study.
Understanding Rheumatoid Arthritis
Authors: Ronald L. Kaye, Ann H. Hammond
Journal: JAMA (1978)

We evaluated a patient education program on understanding rheumatoid arthritis; 94% of those responding to our questionnaire considered the program helpful in increasing their understanding of their condition, and 93% said it enhanced their communication with their family. A total of 85% reported one or more behavioral changes, such as not abusing joints (63%), getting more rest (56%), and using medications more meticulously (48%) after participating in the program. We recommend patient education as an effective means of helping patients understand and hence comply with physicians' instructions, as well as helping patients to assume greater responsibility for their own health care. (<i>JAMA</i>239:2466-2467, 1978)
Staging of Breast Cancer and Survival Rates
Authors: Donald J. Ferguson
Journal: JAMA (1982)

The correlation of staging criteria for mammary carcinoma with the curability of primary and recurrent local and regional lesions was assessed by follow-up after 1,259 consecutive radical mastectomies performed in women under age 70 between 1927 and 1978. Using a staging scheme revised in the light of our experience, the incidence of recurrence by 20 years was 34% ±2.7% for pathological stage I, 65% ±2.6% for stage II, and 83% ±2.5% for stage III. Recurrence after 20 years was observed in one of 178 patients. After treatment of local recurrence, three of 51 patients survived 20 years. By restriction of entry into clinical or pathological stages I and II, currently employed revisions of staging criteria appear to increase survival in all stages, while placing patients with possibly curable lesions in stages III and IV. (<i>JAMA</i>1982;248:1337-1341)
Bacterial Prostatitis vs "Prostatosis"
Authors: Edwin M. Meares
Journal: JAMA (1973)

Chronic bacterial prostatitis, caused primarily by gram-negative bacteria, is a common cause of relapsing urinary tract infection. "Prostatosis," a common condition, is characterized by symptoms that simulate chronic bacterial prostatitis but the urine is sterile and the prostatic fluid cultures are negative. Historical and bacteriological data from 21 consecutive patients with chronic bacterial prostatitis were compared to similar data from 20 consecutive patients with prostatosis. Despite culture of the urethra, midstream urine, and expressed prostatic secretions for neisserial organisms, T-strain<i>Mycoplasma</i>organisms, aerobic bacteria, and anaerobic bacteria, no infectious agent was isolated in cases of prostatosis. Treatment of the two conditions is quite different.
Diethylstilbestrol: Recommended Dosages for Different Categories of Breast Cancer Patients
Authors: Anne C. Carter
Journal: JAMA (1977)

A total of 523 postmenopausal breast cancer patients with progressive disease were entered in a randomized, double-blind study of four dosages of diethylstilbestrol (DES): 1.5,15,150, or 1,500 mg/day. Higher dosages produced significantly (<i>P</i>&lt;.05) higher regression rates: 21% for the 1,500 mg dosage, 17% for the 150 mg dosage, 15% for the 15 mg dosage, and 10% for 1.5 mg dosage. Durations of regressions were similar regardless of the dosages used to induce them. Although the highest dosage produced the highest regression rate overall, selecting the best dosage or treatment of choice for each type of patient based on menopausal age and on dominant metastatic site would result in more regressions. (<i>JAMA</i>237:2079-2085, 1977)
Testicular vein ligation and fertility in men with varicoceles.
Authors: H W Baker, H G Burger, D M de Kretser, B Hudson, G C Rennie, W G Straffon
Journal: BMJ (1985)

Pregnancy rates in 651 subfertile couples in which the man had a varicocele were analysed by life table methods and were not found to be significantly different before and after testicular vein ligation performed in 283 patients. Estimated proportions of couples conceiving were roughly 30% by one year and 45% by two years in both groups. The operation was also not associated with improvement in results of semen analysis. These findings suggest that testicular vein ligation for varicoceles does not improve fertility.
More on Catfish Stings
Authors: Bernard M. Patten
Journal: JAMA (1975)

<h3>To the Editor.—</h3> Dr. Scoggin's article on catfish stings (231:176, 1975) reminds me of my own experience. Last fall, my son Craig and I were catfishing on an estuarine body of water that connects with the Gulf of Mexico. As usual, Craig was catching most of the fish, and when he landed a 30-cm (12-in) catfish he asked me to get it off his hook. As I reached for it, the fish made a sudden leap and stung the end of the fourth finger of my right hand. The linear wound, no more than 4 mm long and 1 mm deep, bled profusely. Following the sting, I felt an instantaneous scalding sensation spread up the finger to involve the hand and the right upper extremity. Rapid involuntary tremor was present in the finger, and random, irregular muscle contractions resembling fasciculations were present in thenar and hypothenar muscles. Six hundred milligrams
Guillain-Barré Syndrome in the United States, 1979-1980 and 1980-1981
Authors: Jonathan E. Kaplan
Journal: JAMA (1982)

An ongoing surveillance program was intensified during the 1979-1980 and the 1980-1981 influenza seasons to determine whether an increased risk of acquiring Guillain-Barré syndrome (GBS) within eight weeks after influenza vaccination existed for adults in the United States who received influenza vaccine, when compared with adults who had not been vaccinated recently. Five hundred twenty-eight cases of GBS with onset between Sept 1 and March 31, including seven following recent vaccination, were reported by participating neurologists in 1979-1980; 459 cases, including 12 following recent vaccination, were reported in 1980-1981. The relative risk of acquiring GBS following influenza vaccination—0.6 in 1979-1980 and 1.4 in 1980-1981—was not significantly different from 1.0 in either season. These results suggest that there was no increased risk of acquiring GBS associated with the influenza vaccines administered during these seasons and that the causative "trigger agent" in the A/New Jersey (swine) influenza vaccine administered in 1976 has not been present in subsequent influenza vaccine preparations. (<i>JAMA</i>1982;248:698-700)
Influenza Vaccination of Elderly Persons
Authors: William H. Barker
Journal: JAMA (1980)

Effectiveness of influenza vaccination in reducing pneumonia and influenza hospitalizations and deaths among elderly members of a prepaid health plan was analyzed retrospectively. Two epidemics caused by the H3N2 subtype of type A influenza were studied. Vaccine derived from the H2N2 subtype of influenza A virus failed to protect against the Hong Kong (H3N2) virus during the 1968-1969 epidemic. Vaccine derived from the A/Hong Kong/68 (H3N2) virus yielded an estimated 72% (31% to 100%) reduction in hospitalization and 87% (52% to 100%) reduction in mortality during the 1972-1973 epidemic caused by A/England/72 (H3N2). These findings are consistent with those reported in vaccinated young persons, and hence it appears they may be broadly generalized. (<i>JAMA</i>1980;244:2547-2549)
Overview of Results of Randomized Clinical Trials in Heart Disease
Authors: Salim Yusuf
Journal: JAMA (1988)

THIS is the second of a two-part article on the results of randomized trials of treatments designed to reduce mortality or major morbidity in heart disease. Our goal is to summarize the results of trials of common treatments on major outcomes in unstable angina, congestive heart failure, primary prevention with aspirin, and risk factor modification. This summary should provide useful background information against which clinicians must consider other information (eg, patient prognosis, risk of side effects, drug interactions, and specific clinical picture) in making decisions about individual patients. We do not deal in either article with trials of coronary artery bypass graft surgery for stable angina, trials of valve replacement, or congenital heart disease. The risk reductions are based on the odds ratio calculated by the Mantel-Haenszel method as applied to combining data from several trials. When event rates are low, the odds ratio and the relative risk are numerically
Pertussis Hospitalizations and Mortality in the United States, 1985-1988
Authors: Roland W. Sutter
Journal: JAMA (1992)

<h3>Objective.</h3> —To determine the magnitude of hospitalizations for pertussis and pertussis mortality and to estimate the total burden of clinically significant pertussis in the United States. <h3>Design.</h3> —Capture-recapture methods for estimating population size from independent surveillance systems were used to analyze morbidity and mortality data from case report forms received at the Centers for Disease Control (CDC) from the states, and compared these data with pertussis hospitalizations compiled from a database of US hospitals participating in the Commission on Professional and Hospital Activities-Professional Activities Survey (CPHA-PAS) and death certificate reports compiled by the National Center for Health Statistics (NCHS). <h3>Population Studied.</h3> —All pertussis hospitalizations and pertussis-related deaths in the United States, 1985 through 1988. <h3>Results.</h3> —We estimated that 13557 pertussis hospitalizations (95% confidence interval [CI], 12953 to 14162) and 98 pertussis deaths had occurred during the 4-year study period (an average of more than 3300 hospitalizations and 25 deaths per year). The completeness of reporting hospitalizations to the CDC was 32% and to the CPHA-PAS, 23%, while the completeness of reporting pertussis deaths to the CDC was 33% and to NCHS, 23%. Patients who were hospitalized with pertussis and reported to CDC were at a higher risk for developing pneumonia (31.0% vs 20.0%, relative risk [RR], 1.6; 95% CI, 1.4 to 1.7), seizures (3.7% vs 2.1%; RR, 1.9; 95% CI, 1.4 to 2.5) and encephalitis (1.2% vs 0.2%; RR, 5.3; 95% CI, 2.4 to 11.6) compared with patients recorded in the CPHA-PAS system. <h3>Conclusions.</h3> —Our study suggests that there is substantial underreporting of pertussis, that severe complications of pertussis (including hospitalizations) are reported preferentially to the CDC, and that the national health impact of pertussis based on these indicators is considerably higher than previously published reports have suggested. (<i>JAMA</i>. 1992;267:386-391)
Children With an Increased Lead Burden
Authors: Siegfried M. Pueschel
Journal: JAMA (1972)

In a house-to-house survey of an impoverished section of Boston, preschool children were studied in regard to lead poisoning with the use of a simple and inexpensive screening procedure based upon the analysis of lead in hair. Ninety-eight of 705 children screened in this fashion were found to have an increased lead burden. Chelation therapy was administered and environmental elimination of exposure to leadcontaining substances was initiated. Fifty-eight children with an increased lead burden underwent comprehensive study and 1 1/2 years later reexamination took place: minor neurological dysfunction and various forms of motor impairment were observed in 22% to 27% of the children during each evaluation. Initial psychological assessment revealed low average mental abilities in the majority of children and 1 1/2 years later a significant increase in certain areas of intellectual functioning was noted.
Live Attenuated Rubella Virus Vaccines Prepared in Duck Embryo Cell Culture
Authors: Robert E. Weibel
Journal: JAMA (1968)

Duck embryo cell culture rubella virus vaccines prepared with the HPV-77 (Meyer-Parkman) and the Merck (B-level attenuation) strains of virus were evaluated in a large-scale family study in the open community and in an institution. Of 265 initially seronegative children vaccinated with the HPV-77 virus in duck embryo cell culture, 97% responded serologically with a geometric mean hemagglutination-inhibiting (HI) titer of 1:53.2. There was no apparent clinical illness and no serologic evidence for contact spread to 262 susceptible siblings or to 34 maternal contacts. The performance of the Merck B-level vaccine in duck embryo cell culture in the smaller institutional study was essentially the same as that of the HPV-77 except that the mean HI titer was almost three times as great (1:148.3). Both vaccines proved safe and efficacious in children, and community studies are in progress in larger numbers of persons.
Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma
Authors: François-Xavier Danlos, Matthieu Texier, Bastien Job, Severine Mouraud, Lydie Cassard, Capucine Baldini, Andrea Varga, Andrey A. Yurchenko, Audrey Rabeau, Stéphane Champiat, Diane Letourneur, Delphine Bredel, Sandrine Susini, Yuna Blum, Aurelien Parpaleix, Cedric Parlavecchio, Lambros Tselikas, Jean-Eudes Fahrner, Anne-Gaelle Goubet, Mathieu Rouanne, Saloomeh Rafie, Alae Abbassi, Ines Kasraoui, Marie Breckler, Siham Farhane, Samy Ammari, Salim Laghouati, Anas Gazzah, Ludovic Lacroix, Benjamin Besse, Nathalie Droin, Marc Deloger, Sophie Cotteret, Julien Adam, Laurence Zitvogel, Sergey I. Nikolaev, Nathalie Chaput, Christophe Massard, Jean-Charles Soria, Carlos Gomez-Roca, Gerard Zalcman, David Planchard, Aurelien Marabelle
Journal: Cancer Discovery (2023)

Cancer immunotherapy combinations have recently been shown to improve the overall survival of advanced mesotheliomas, especially for patients responding to those treatments. We aimed to characterize the biological correlates of malignant pleural mesotheliomas' primary resistance to immunotherapy and antiangiogenics by testing the combination of pembrolizumab, an anti-PD-1 antibody, and nintedanib, a pan-antiangiogenic tyrosine kinase inhibitor, in the multicenter PEMBIB trial (NCT02856425). Thirty patients with advanced malignant pleural mesothelioma were treated and explored. Unexpectedly, we found that refractory patients were actively recruiting CD3+CD8+ cytotoxic T cells in their tumors through CXCL9 tumor release upon treatment. However, these patients displayed high levels of somatic copy-number alterations in their tumors that correlated with high blood and tumor levels of IL6 and CXCL8. Those proinflammatory cytokines resulted in higher tumor secretion of VEGF and tumor enrichment in regulatory T cells. Advanced mesothelioma should further benefit from stratified combination therapies adapted to their tumor biology. Sequential explorations of fresh tumor biopsies demonstrated that mesothelioma resistance to anti-PD-1 + antiangiogenics is not due to a lack of tumor T-cell infiltration but rather due to adaptive immunosuppressive pathways by tumors, involving molecules (e.g., IL6, CXCL8, VEGF, and CTLA4) that are amenable to targeted therapies. This article is highlighted in the In This Issue feature, p. 799.
B cell–intrinsic requirement for WNK1 kinase in antibody responses in mice
Authors: Darryl A. Hayward, Lesley Vanes, Stefanie Wissmann, Sujana Sivapatham, Harald Hartweger, Joshua Biggs O’May, Leonard L. de Boer, Richard Mitter, Robert Köchl, Jens V. Stein, Victor L.J. Tybulewicz
Journal: The Journal of Experimental Medicine (2023)

Migration and adhesion play critical roles in B cells, regulating recirculation between lymphoid organs, migration within lymphoid tissue, and interaction with CD4+ T cells. However, there is limited knowledge of how B cells integrate chemokine receptor and integrin signaling with B cell activation to generate efficient humoral responses. Here, we show that the WNK1 kinase, a regulator of migration and adhesion, is essential in B cells for T-dependent and -independent antibody responses. We demonstrate that WNK1 transduces signals from the BCR, CXCR5, and CD40, and using intravital imaging, we show that WNK1 regulates migration of naive and activated B cells, and their interactions with T cells. Unexpectedly, we show that WNK1 is required for BCR- and CD40-induced proliferation, acting through the OXSR1 and STK39 kinases, and for efficient B cell–T cell collaboration in vivo. Thus, WNK1 is critical for humoral immune responses, by regulating B cell migration, adhesion, and T cell–dependent activation.
Obstructive nephropathy as a result of retroperitoneal fibrosis
Authors: T M Demko, J R Diamond, J Groff
Journal: Journal of the American Society of Nephrology (1997)

Retroperitoneal fibrosis is a rare disease, typically with an insidious clinical course. It is thought that this disease process is perhaps an exaggerated reaction to an inciting inflammatory event. In this study, a case of retroperitoneal fibrosis is reported, in which the patient presented with typical symptoms of retroperitoneal fibrosis, along with some atypical vasculitic symptomatology. Retroperitoneal fibrosis is a disease process with an unknown etiology, which has been observed to be associated with a number of different possible inciting factors. Two factors that have been documented in the literature as being associated with retroperitoneal fibrosis include the use of beta-blocking agents, and connective tissue disease processes such as systemic lupus erythematosus. The patient discussed was using beta-blocker medication and also had signs and symptoms suggestive of a lupus syndrome. There are no reported cases of the combined association of beta-blocker usage, lupus, and retroperitoneal fibrosis.
Randomized Phase III Trial of Ganitumab With Interval-Compressed Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma: A Report From the Children's Oncology Group
Authors: Steven G. DuBois, Mark D. Krailo, Julia Glade-Bender, Allen Buxton, Nadia Laack, R. Lor Randall, Helen X. Chen, Nita L. Seibel, Matthew Boron, Stephanie Terezakis, Christine Hill-Kayser, Andrea Hayes, Joel M. Reid, Lisa Teot, Dinesh Rakheja, Richard Womer, Carola Arndt, Stephen L. Lessnick, Brian D. Crompton, E. Anders Kolb, Heike Daldrup-Link, Eric Eutsler, Damon R. Reed, Katherine A. Janeway, Richard G. Gorlick
Journal: Journal of Clinical Oncology (2023)

Monoclonal antibodies directed against insulin-like growth factor-1 receptor (IGF-1R) have shown activity in patients with relapsed Ewing sarcoma. The primary objective of Children's Oncology Group trial AEWS1221 was to determine if the addition of the IGF-1R monoclonal antibody ganitumab to interval-compressed chemotherapy improves event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma.
A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas
Authors: Mrinal M. Gounder, Todd M. Bauer, Gary K. Schwartz, Amy M. Weise, Patricia LoRusso, Prasanna Kumar, Ben Tao, Ying Hong, Parul Patel, Yasong Lu, Arnaud Lesegretain, Vijaya G. Tirunagaru, Feng Xu, Robert C. Doebele, David S. Hong
Journal: Journal of Clinical Oncology (2023)

This study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of milademetan, a small-molecule murine double minute-2 (MDM2) inhibitor, in patients with advanced cancers.
Low-Dose Immunotherapy Plus Triple Metronomic Chemotherapy for Head and Neck Cancer
Authors: Dun-Chang Mo, Jian-Feng Huang, Peng-Hui Luo
Journal: Journal of Clinical Oncology (2023)

Journal of Clinical Oncology by Patil et al, 1 who reported that compared with triple metronomic chemotherapy (TMC, consisting of capsule celecoxib 200 mg twice daily, weekly methotrexate 9 mg/m 2 once a week, and erlotinib 150 mg once daily), the addition of low-dose nivolumab (20 mg flat dose intravenously once every 3 weeks) to TMC (TMC-I) was associated with significantly improved overall survival (OS) in the treatment of advanced head and neck squamous cell carcinoma (HNSCC).The median OS for TMC and TMC-I was 6.7 and 10.1 months, respectively (hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P 5 .0036).The authors concluded that the addition of low dose nivolumab to metronomic chemotherapy is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.Despite the exciting results, we believe that there is an aspect that deserves close attention.
Impact of the HLA Immunopeptidome on Survival of Leukemia Patients After Unrelated Donor Transplantation
Authors: Pietro Crivello, Esteban Arrieta-Bolaños, Meilun He, Tao Wang, Stephanie Fingerson, Shahinaz M. Gadalla, Sophie Paczesny, Steven G.E. Marsh, Stephanie J. Lee, Stephen R. Spellman, Yung-Tsi Bolon, Katharina Fleischhauer
Journal: Journal of Clinical Oncology (2023)

Immunopeptidome divergence between mismatched HLA-DP is a determinant of T-cell alloreactivity and clinical tolerability after fully HLA-A, -B, -C, -DRB1, -DQB1 matched unrelated donor hematopoietic cell transplantation (UD-HCT). Here, we tested this concept in HLA-A, -B, and -C disparities after single class I HLA-mismatched UD-HCT.
Dexrazoxane and Long-Term Heart Function in Survivors of Childhood Cancer
Authors: Eric J. Chow, Sanjeev Aggarwal, David R. Doody, Richard Aplenc, Saro H. Armenian, K. Scott Baker, Smita Bhatia, Nancy Blythe, Steven D. Colan, Louis S. Constine, David R. Freyer, Lisa M. Kopp, Caroline Laverdière, Wendy M. Leisenring, Nao Sasaki, Lynda M. Vrooman, Barbara L. Asselin, Cindy L. Schwartz, Steven E. Lipshultz
Journal: Journal of Clinical Oncology (2023)

For survivors of childhood cancer treated with doxorubicin, dexrazoxane is cardioprotective for at least 5 years. However, longer-term data are lacking.